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Stimulation of lipolysis enhances the rate of cholesterol efflux to HDL in adipocytes

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Abstract

Adipose tissue constitutes a major location for cholesterol storage and, as such, it may play a role in the regulation of circulating cholesterol levels. A possible metabolic link between the lipolytic activity of adipocytes and their ability to release cholesterol to reconstituted human high density lipoprotein, HDL, was investigated in 3T3-L1 adipocytes. In the presence of HDL, composed of human apoA-I and phosphatidylcholine, adipocytes release cholesterol in a lipoprotein-dose and time dependent fashion. β-adrenergic activation of the lipolysis promotes a 22% increase in the extent of cholesterol efflux to reconstituted discoidal HDL particles. Activation of lipolysis promotes a rapid decrease in the cholesterol content of the plasma membrane and a concomitant increase in lipid droplet cholesterol. This change is independent of the presence of HDL. Activation of the lipolysis does not affect the levels of ABCA1 and SR-BI. Therefore, the enhancement of cholesterol efflux is not due to the level of plasma membrane cholesterol, or to the levels of the cholesterol transporters ABCA1 and scavenger receptor SR-BI. Brefeldin A did not affect the rate of cholesterol efflux under basal lipolytic conditions, but it abolished the lipolysis-dependent enhancement of cholesterol efflux to HDL. This study suggests that activation of lipolysis is accompanied by an increase in BFA-sensitive vesicular transport that in turn enhances cholesterol efflux to HDL. The study supports a metabolic link between the lipolytic activity of adipocytes and the rate of cellular cholesterol efflux to HDL.

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Acknowledgements

The authors would like to thank Dr. Eric A. Lehoux for his valuable help in the tissue culture studies. This study was funded by Oklahoma State Experiment Station and NIH Grants GM 55622 and GM 64677.

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Correspondence to Jose L. Soulages.

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Verghese, P.B., Arrese, E.L. & Soulages, J.L. Stimulation of lipolysis enhances the rate of cholesterol efflux to HDL in adipocytes. Mol Cell Biochem 302, 241–248 (2007). https://doi.org/10.1007/s11010-007-9447-0

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  • DOI: https://doi.org/10.1007/s11010-007-9447-0

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